A new study suggests that previously noted low rates of successful hepatitis
C virus (HCV) therapy in African Americans are in large part due to very
early differences in the antiviral activity induced by interferon. The study
is published in the April 15 issue of the Journal of Infectious Diseases,
now available online.

More than 3 million Americans are infected with HCV, and in some countries
more than 10 percent of the population is infected. Chronic HCV infection is
the leading cause of liver failure worldwide. Response to standard therapy
with peginterferon and ribavirin varies widely. Those infected with one
strain of the virus - genotype 1 - are the least likely to have a successful
response to therapy, known as a sustained virological response (SVR). About
one-half of patients infected with genotype 1 do not achieve SVR.

Studies have shown that African Americans have consistently lower rates of
SVR to interferon-based therapy, compared to Caucasian Americans. A recent
study of those with chronic genotype 1 HCV infection found that only 28
percent of African American patients attained SVR, compared with 52 percent
in Caucasian Americans. This new study shows that the variation in therapy
responsiveness between African Americans and Caucasian Americans can be
partly explained by differences in viral response noted as early as one to
two days after the first dose of peginterferon.

The study, conducted by a collaborative group of eight medical centers
throughout the United States, monitored 341 patients with chronic HCV,
genotype 1, who underwent therapy with peginterferon and ribavirin for at
least 24 weeks. It focused on response rates to interferon therapy within
the first 28 days of therapy, noting viral factors such as HCV RNA levels
and host factors such as race, gender, and weight.

Results showed that HCV RNA levels decreased in almost all patients, and
that the degree and pattern of decrease, as expected, was different between
African and Caucasian Americans. Most important was the new finding that
these differences were statistically significant by day 2 of treatment, and
that this early viral kinetic measurement was a reliable predictor of
ultimate SVR rates. After 28 days of treatment, 22 percent of Caucasian
Americans, but only 12 percent of African Americans, were HCV RNA negative.

These findings are particularly important because they point toward the
presence of some block or defect in the immediate antiviral response of
those who do not respond to therapy. As the authors summarize, "The
underlying cause of virological non-response and the reasons why it is more
common among African Americans than Caucasian Americans are not clear. [But]
the current analyses demonstrated that these differences are fundamentally
biologic and become apparent within 24 to 48 hours of starting therapy." As
a next step, future research should focus on these host biologic factors
that are induced by interferon in an attempt to improve therapy response
rates.

In an accompanying editorial, Andrew W. Tai, MD, PhD, and Raymond T. Chung,
MD, of Massachusetts General Hospital agree that the findings will prove
vital for future research into HCV, remarking, "[this study] demonstrates
that the low rates of SVR in African American patients in response to IFN-based
therapy appear to result, in large part, from impaired early viral kinetics.
Further studies are necessary to uncover the relevant mechanisms that
underlie this defect in IFN signaling… with the hope that such mechanisms
can be manipulated to restore interferon responsiveness in the otherwise
nonresponsive host."